Commentary

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Diabetes mellitus and its management have become the center of controversy in recent years. More emphasis is being placed on the potential for adverse cardiovascular outcomes with more aggressive glycemic control as well as on the potential for adverse cardiovascular events with newer antidiabetic therapies, and less on the importance of glycemic control, particularly early in the disease course.

See related article

Although it is important to take new data into consideration when managing diabetes, it appears that the results of recent clinical trials are being misinterpreted and incorrectly applied to the wrong patient populations, and in the process, the results of older landmark clinical trials are being neglected. Inadequate glycemic control not only plays a role in cardiovascular risk, it also remains the leading cause of blindness, kidney failure, and nontraumatic lower-limb amputations in the United States.¹

Although we need to recognize the potential for adverse cardiovascular outcomes with diabetes and its management, we cannot lose sight of the big picture—ie, that inadequate glycemic control confers both microvascular and macrovascular risk, and that the available data show that restoring near-euglycemia in patients with diabetes considerably reduces the risk of microvascular and macrovascular complications.

Several recently published clinical trials—the Action to Control Cardiovascular Risk in Diabetes (ACCORD),² the Veterans Affairs Diabetes Trial (VADT),³ and the Action in Diabetes and Vascular Disease (ADVANCE)⁴—failed to demonstrate improved cardiovascular outcomes with improved glycemic control. However, we should not take this to mean that glycemic control is unimportant.

In this article, we will discuss why the results of these recent clinical trials are not valid for the general population of patients with diabetes. We will review evidence from landmark clinical trials that clearly demonstrates that better glycemic control reduces both microvascular and macrovascular complications of diabetes (the “glucose hypothesis”). We contend that excellent glycemic control clearly decreases the microvascular complications of diabetes, and that results from long-term follow-up studies in both type 1 and type 2 diabetes show reduced rates of heart attack and stroke in patients treated intensively earlier in the course of their disease.^5,6

EVIDENCE FOR THE GLUCOSE HYPOTHESIS

Diabetes Control and Complications Trial

The first major trial demonstrating that improved glycemic control provides benefit was the Diabetes Control and Complications Trial (DCCT).⁷ This study enrolled 1,441 patients with insulin-dependent diabetes mellitus, 726 of whom had no retinopathy at baseline (the primary-prevention cohort) and 715 of whom had mild retinopathy (the secondary-intervention cohort).

Patients were randomly assigned to intensive therapy (three or more insulin injections per day or an insulin pump) or to conventional therapy with one or two daily insulin injections. They were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.

During the study, the hemoglobin A_1c level averaged 9% in the control group and 7% in the intensively treated group. The cumulative incidence of retinopathy was defined as a change of three steps or more on fundus photography that was sustained over a 6-month period.

Effect on retinopathy. At study completion, the cumulative incidence of retinopathy in the intensive-therapy group was approximately 50% less than in the conventional-therapy group. Intensive therapy reduced the adjusted mean risk of retinopathy by 76% (95% confidence interval [CI] 62%–85%) in the primary-prevention cohort. In the secondary-prevention cohort, intensive therapy reduced the average risk of progression by 54% (95% CI 39%–66%). Intensive therapy reduced the adjusted risk of proliferative or severe nonproliferative retinopathy by 47% (P = .011) and that of treatment with photocoagulation by 56% (P = .002).

Effect on nephropathy. Intensive therapy reduced the mean adjusted risk of microalbuminuria by 34% (P = .04) in the primary-prevention cohort and by 43% (P = .001) in the secondary-intervention cohort. The risk of macroalbuminuria was reduced by 56% (P = .01) in the secondary-intervention cohort.

Effect on neuropathy. In the patients in the primary-prevention cohort who did not have neuropathy at baseline, intensive therapy reduced the incidence of neuropathy at 5 years by 69% (to 3%, vs 10% in the conventional-therapy group; P = .006). Similarly, in the secondary-intervention cohort, intensive therapy reduced the incidence of clinical neuropathy at 5 years by 57% (to 7%, vs 16%; P < .001).

Effect on macrovascular events. In the initial trial, a nonsignificant 41% reduction in combined cardiovascular and peripheral vascular disease events was observed.

DCCT long-term follow-up

After DCCT concluded, the control and treatment groups’ hemoglobin A_1c levels converged to approximately 8%. The two groups were then followed to determine the long-term effects of their prior separation of glycemic levels on micro- and macrovascular out comes.⁵ More than 90% of the original DCCT patients were followed for a mean of 17 years.

Intensive treatment reduced the risk of any cardiovascular disease event by 42% (95% CI 9%–63%; P = .02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57% (95% CI 12%– 79%; P = .02). This result was observed despite separation of glucose control in the two groups only for the first 6.5 years. This beneficial effect of intensive early glycemic control has been termed metabolic memory.

United Kingdom Prospective Diabetes Study

A second major trial, the United Kingdom Prospective Diabetes Study (UKPDS),⁸ assessed the effect of excellent diabetes control on diabetes complications in patients with type 2 diabetes. A total of 3,867 patients newly diagnosed with type 2 diabetes, median age 54, who after 3 months of diet treatment had mean fasting plasma glucose concentrations of 110 to 270 mg/dL, were randomly assigned to an intensive policy (with a sulfonylurea or insulin or, if overweight, metformin) or a conventional policy with diet. The aim in the intensive group was a fasting plasma glucose less than 108 mg/dL. In the conventional group, the aim was the best achievable fasting plasma glucose with diet alone; drugs were added only if there were hyperglycemic symptoms or a fasting plasma glucose greater than 270 mg/dL.

Over 10 years, the median hemoglobin A_1c level was 7.0% (interquartile range 6.2%–8.2%) in the intensive group compared with 7.9% (6.9%–8.8%) in the conventional group. Compared with the conventional group, the risk of any diabetes-related end point was 12% lower in the intensive group (95% CI 1%–21%, P = .029), the risk of any diabetes-related death was 10% lower (−11% to 27%, P = .34), and the rate of all-cause mortality was 6% lower (−10% to 20%, P = .44). Most of the reduction in risk of any diabetes-related end point was from a 25% risk reduction (95% CI 7%–40%, P = .0099) in microvascular end points, including the need for retinal photocoagulation.

UKPDS long-term follow-up

In 2008, Holman et al published the results of long-term follow-up of patients included in the UKPDS.⁶ In posttrial monitoring, 3,277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires.

Between-group differences in hemoglobin A_1c levels were lost after the first year. However, in the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P = .04) and microvascular disease (24%, P = .001), while risk reductions for myocardial infarction (15%, P = .01) and death from any cause (13%, P = .007) emerged over time as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P = .01), myocardial infarction (33%, P = .005), and death from any cause (27%, P = .002).

The long-term follow-up to the UKPDS, like the long-term follow-up to the DCCT, demonstrated metabolic memory: that is, despite an early loss of glycemic differences after completion of the trial, a continued reduction in microvascular risk and an emergent risk reduction for myocardial infarction and death from any cause were observed.

These long-term randomized prospective trials in patients with type 1 and type 2 diabetes clearly show that the glucose hypothesis is in fact correct: intensive glucose control lowers the risk of both microvascular and macrovascular complications of diabetes.

IS THERE DISCORDANCE BETWEEN OLDER AND MORE RECENT TRIALS?

If the results of these older landmark clinical trials are true, why did the more recent clinical trials fail to show cardiovascular benefit with stricter glycemic control, and in one trial² demonstrate the potential for harm? (ACCORD² found an increased death rate in patients who received intensive therapy, targeting a hemoglobin A_1c below 6.0%.)

The answer lies in the populations studied. ACCORD,² VADT,³ and ADVANCE⁴ were performed in older patients with prior cardiac events or with several risk factors for cardiovascular events. The study populations were picked to increase the number of cardiac events in a short time frame. Therefore, extrapolating the results of these studies to the younger population of patients with diabetes, most of whom have yet to develop macrovascular disease, is inappropriate.

The available evidence suggests that early aggressive management of diabetes reduces the risk of macrovascular disease, but that this benefit is delayed. In the UKPDS and DCCT trials, it took 10 to 17 years to show cardiac benefit in younger patients.

The results of ACCORD,² VADT,³ and ADVANCE⁴ are important when considered in the correct clinical context. Two of these trials did demonstrate some microvascular benefit as a result of better glycemic control in older patients, many of whom had longstanding diabetes. These studies suggest that, in patients who already have established cardiovascular disease or have several risk factors for cardiovascular events, a less-strict glycemic target may be warranted.

These trials should not be interpreted as saying that glycemic control is unimportant in older patients at higher risk. Rather, they suggest that an individualized approach to diabetes management, supported by the most recent American Diabetes Association guidelines,⁹ is more appropriate.

Physicians may reasonably suggest a stricter A_1c goal (ie, < 6.5%) in certain patients if it can be achieved without significant hypoglycemia. Stricter glycemic targets would seem appropriate in patients recently diagnosed with diabetes, those who have a long life expectancy, and those who have not yet developed significant cardiovascular disease.⁹

However, in patients who already have developed advanced microvascular and macrovascular complications, who have long-standing diabetes, who have a history of severe hypoglycemia (or hypoglycemia unawareness), or who have a limited life expectancy or numerous adverse comorbidities, a less strict glycemic target (hemoglobin A_1c < 8%) may be more appropriate.⁹

CARDIOVASCULAR RISK, HYPOGLYCEMIA, AND ATTAINING GLYCEMIC TARGETS

Metformin, in the absence of contraindications or intolerability, is generally the recommended first-line therapy to manage glycemia in patients with type 2 diabetes mellitus.^10,11 However, there are only limited data to direct clinicians as to which antidiabetic medication to use if further therapy is required to obtain glycemic control.

Much of the cardiovascular and mortality risk associated with aggressive diabetes management (ie, lower A_1c targets) is related to hypoglycemia. Thus, antidiabetic therapies that pose no risk or only a low risk of hypoglycemia should be chosen, particularly in older patients and in those with known cardiovascular disease. This may allow for better glycemic control without the risk of hypoglycemia and adverse cardiovascular outcomes.

However, in practice, clinicians continue to use a sulfonylurea as the second-line agent. Although sulfonylureas may appear to be a great option because of their low cost, they are associated with a higher risk of hypoglycemic episodes than other classes of diabetes drugs. We need to consider the frequency and cost of hypoglycemic episodes and the potential morbidity associated with them, because these episodes are a barrier to our efforts to achieve better glycemic control.

Budnitz et al¹² reported that from 2007 through 2009, in US adults age 65 and older, insulins were implicated in 13.9% of hospitalizations related to adverse drug events, and oral hypoglycemic agents (ie, insulin secretagogues) in 10.7%.

Quilliam et al¹³ reported that hypoglycemia resulted in a mean cost of $17,564 for an inpatient admission, $1,387 for an emergency department visit, and $394 for an outpatient visit. Thus, the cost savings associated with prescribing a sulfonylurea vs one of the newer oral antidiabetic agents that do not increase the risk of hypoglycemia (unless used concurrently with insulin or an insulin secretagogue) can quickly be eroded by severe hypoglycemic episodes requiring medical care.

Moreover, once patients start to experience hypoglycemic episodes, they are very reluctant, as are their physicians, to intensify therapy, even if it is indicated by their elevated A_1c.

There are now seven classes of oral antidiabetic therapies other than insulin secretagogues (ie, other than sulfonylureas and the meglitinides nateglinide and repaglinide), as well as a few noninsulin injectable therapies (glucagon-like peptide-1 agonists), that are not associated with hypoglycemia. We believe these agents should be tried before prescribing an agent that carries the risk of hypoglycemia (ie, sulfonylureas).

If agents that do not cause hypoglycemia are used, more-aggressive glycemic targets may be achieved safely. The ACCORD study,² which included patients at high cardiovascular risk and aimed at an aggressive glycemic target of 6%, may have yielded much different results had agents that carry a high risk of hypoglycemia been excluded.

Of importance, cardiovascular risk is also influenced by the common comorbidities seen in patients with diabetes, such as hypertension and hypercholesterolemia. Intensive, multifactorial interventions that address not only glycemic control but also blood pressure and lipids and that include low-dose aspirin therapy have been shown to lower the risk of death from cardiovascular causes and the risk of cardiovascular events.¹⁴ Likewise, smoking cessation is very important in reducing cardiovascular risk, especially in patients with diabetes.¹⁵

CLINICAL TRIALS IN CONTEXT

In conclusion, there is more to diabetes management than cardiovascular complications. Clearly, improved glycemic control decreases the risk of retinopathy, nephropathy, and neuropathy in patients with type 1 and type 2 diabetes. The DCCT and UKPDS extension studies further found that excellent glycemic control decreases rates of cardiac events.

The best way to treat diabetes may be different in otherwise healthy younger patients who have yet to develop significant complications than it is in older patients known to have cardiovascular disease or several risk factors for cardiovascular events. The available evidence suggests it would be reasonable to aim for stricter glycemic targets in the younger patients and less stringent targets in the older patients, particularly in those with long-standing diabetes who have already developed significant micro- and macrovascular complications.

We should interpret clinical trials within their narrow clinical context, emphasizing the actual population of patients included in the study, so as to avoid the inappropriate extrapolation of the results to all.

Diabetes mellitus and its management have become the center of controversy in recent years. More emphasis is being placed on the potential for adverse cardiovascular outcomes with more aggressive glycemic control as well as on the potential for adverse cardiovascular events with newer antidiabetic therapies, and less on the importance of glycemic control, particularly early in the disease course.

See related article

Although it is important to take new data into consideration when managing diabetes, it appears that the results of recent clinical trials are being misinterpreted and incorrectly applied to the wrong patient populations, and in the process, the results of older landmark clinical trials are being neglected. Inadequate glycemic control not only plays a role in cardiovascular risk, it also remains the leading cause of blindness, kidney failure, and nontraumatic lower-limb amputations in the United States.¹

Although we need to recognize the potential for adverse cardiovascular outcomes with diabetes and its management, we cannot lose sight of the big picture—ie, that inadequate glycemic control confers both microvascular and macrovascular risk, and that the available data show that restoring near-euglycemia in patients with diabetes considerably reduces the risk of microvascular and macrovascular complications.

Several recently published clinical trials—the Action to Control Cardiovascular Risk in Diabetes (ACCORD),² the Veterans Affairs Diabetes Trial (VADT),³ and the Action in Diabetes and Vascular Disease (ADVANCE)⁴—failed to demonstrate improved cardiovascular outcomes with improved glycemic control. However, we should not take this to mean that glycemic control is unimportant.

In this article, we will discuss why the results of these recent clinical trials are not valid for the general population of patients with diabetes. We will review evidence from landmark clinical trials that clearly demonstrates that better glycemic control reduces both microvascular and macrovascular complications of diabetes (the “glucose hypothesis”). We contend that excellent glycemic control clearly decreases the microvascular complications of diabetes, and that results from long-term follow-up studies in both type 1 and type 2 diabetes show reduced rates of heart attack and stroke in patients treated intensively earlier in the course of their disease.^5,6

EVIDENCE FOR THE GLUCOSE HYPOTHESIS

Diabetes Control and Complications Trial

The first major trial demonstrating that improved glycemic control provides benefit was the Diabetes Control and Complications Trial (DCCT).⁷ This study enrolled 1,441 patients with insulin-dependent diabetes mellitus, 726 of whom had no retinopathy at baseline (the primary-prevention cohort) and 715 of whom had mild retinopathy (the secondary-intervention cohort).

Patients were randomly assigned to intensive therapy (three or more insulin injections per day or an insulin pump) or to conventional therapy with one or two daily insulin injections. They were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.

During the study, the hemoglobin A_1c level averaged 9% in the control group and 7% in the intensively treated group. The cumulative incidence of retinopathy was defined as a change of three steps or more on fundus photography that was sustained over a 6-month period.

Effect on retinopathy. At study completion, the cumulative incidence of retinopathy in the intensive-therapy group was approximately 50% less than in the conventional-therapy group. Intensive therapy reduced the adjusted mean risk of retinopathy by 76% (95% confidence interval [CI] 62%–85%) in the primary-prevention cohort. In the secondary-prevention cohort, intensive therapy reduced the average risk of progression by 54% (95% CI 39%–66%). Intensive therapy reduced the adjusted risk of proliferative or severe nonproliferative retinopathy by 47% (P = .011) and that of treatment with photocoagulation by 56% (P = .002).

Effect on nephropathy. Intensive therapy reduced the mean adjusted risk of microalbuminuria by 34% (P = .04) in the primary-prevention cohort and by 43% (P = .001) in the secondary-intervention cohort. The risk of macroalbuminuria was reduced by 56% (P = .01) in the secondary-intervention cohort.

Effect on neuropathy. In the patients in the primary-prevention cohort who did not have neuropathy at baseline, intensive therapy reduced the incidence of neuropathy at 5 years by 69% (to 3%, vs 10% in the conventional-therapy group; P = .006). Similarly, in the secondary-intervention cohort, intensive therapy reduced the incidence of clinical neuropathy at 5 years by 57% (to 7%, vs 16%; P < .001).

Effect on macrovascular events. In the initial trial, a nonsignificant 41% reduction in combined cardiovascular and peripheral vascular disease events was observed.

DCCT long-term follow-up

After DCCT concluded, the control and treatment groups’ hemoglobin A_1c levels converged to approximately 8%. The two groups were then followed to determine the long-term effects of their prior separation of glycemic levels on micro- and macrovascular out comes.⁵ More than 90% of the original DCCT patients were followed for a mean of 17 years.

Intensive treatment reduced the risk of any cardiovascular disease event by 42% (95% CI 9%–63%; P = .02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57% (95% CI 12%– 79%; P = .02). This result was observed despite separation of glucose control in the two groups only for the first 6.5 years. This beneficial effect of intensive early glycemic control has been termed metabolic memory.

United Kingdom Prospective Diabetes Study

A second major trial, the United Kingdom Prospective Diabetes Study (UKPDS),⁸ assessed the effect of excellent diabetes control on diabetes complications in patients with type 2 diabetes. A total of 3,867 patients newly diagnosed with type 2 diabetes, median age 54, who after 3 months of diet treatment had mean fasting plasma glucose concentrations of 110 to 270 mg/dL, were randomly assigned to an intensive policy (with a sulfonylurea or insulin or, if overweight, metformin) or a conventional policy with diet. The aim in the intensive group was a fasting plasma glucose less than 108 mg/dL. In the conventional group, the aim was the best achievable fasting plasma glucose with diet alone; drugs were added only if there were hyperglycemic symptoms or a fasting plasma glucose greater than 270 mg/dL.

Over 10 years, the median hemoglobin A_1c level was 7.0% (interquartile range 6.2%–8.2%) in the intensive group compared with 7.9% (6.9%–8.8%) in the conventional group. Compared with the conventional group, the risk of any diabetes-related end point was 12% lower in the intensive group (95% CI 1%–21%, P = .029), the risk of any diabetes-related death was 10% lower (−11% to 27%, P = .34), and the rate of all-cause mortality was 6% lower (−10% to 20%, P = .44). Most of the reduction in risk of any diabetes-related end point was from a 25% risk reduction (95% CI 7%–40%, P = .0099) in microvascular end points, including the need for retinal photocoagulation.

UKPDS long-term follow-up

In 2008, Holman et al published the results of long-term follow-up of patients included in the UKPDS.⁶ In posttrial monitoring, 3,277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires.

Between-group differences in hemoglobin A_1c levels were lost after the first year. However, in the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P = .04) and microvascular disease (24%, P = .001), while risk reductions for myocardial infarction (15%, P = .01) and death from any cause (13%, P = .007) emerged over time as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P = .01), myocardial infarction (33%, P = .005), and death from any cause (27%, P = .002).

The long-term follow-up to the UKPDS, like the long-term follow-up to the DCCT, demonstrated metabolic memory: that is, despite an early loss of glycemic differences after completion of the trial, a continued reduction in microvascular risk and an emergent risk reduction for myocardial infarction and death from any cause were observed.

These long-term randomized prospective trials in patients with type 1 and type 2 diabetes clearly show that the glucose hypothesis is in fact correct: intensive glucose control lowers the risk of both microvascular and macrovascular complications of diabetes.

IS THERE DISCORDANCE BETWEEN OLDER AND MORE RECENT TRIALS?

If the results of these older landmark clinical trials are true, why did the more recent clinical trials fail to show cardiovascular benefit with stricter glycemic control, and in one trial² demonstrate the potential for harm? (ACCORD² found an increased death rate in patients who received intensive therapy, targeting a hemoglobin A_1c below 6.0%.)

The answer lies in the populations studied. ACCORD,² VADT,³ and ADVANCE⁴ were performed in older patients with prior cardiac events or with several risk factors for cardiovascular events. The study populations were picked to increase the number of cardiac events in a short time frame. Therefore, extrapolating the results of these studies to the younger population of patients with diabetes, most of whom have yet to develop macrovascular disease, is inappropriate.

The available evidence suggests that early aggressive management of diabetes reduces the risk of macrovascular disease, but that this benefit is delayed. In the UKPDS and DCCT trials, it took 10 to 17 years to show cardiac benefit in younger patients.

The results of ACCORD,² VADT,³ and ADVANCE⁴ are important when considered in the correct clinical context. Two of these trials did demonstrate some microvascular benefit as a result of better glycemic control in older patients, many of whom had longstanding diabetes. These studies suggest that, in patients who already have established cardiovascular disease or have several risk factors for cardiovascular events, a less-strict glycemic target may be warranted.

These trials should not be interpreted as saying that glycemic control is unimportant in older patients at higher risk. Rather, they suggest that an individualized approach to diabetes management, supported by the most recent American Diabetes Association guidelines,⁹ is more appropriate.

Physicians may reasonably suggest a stricter A_1c goal (ie, < 6.5%) in certain patients if it can be achieved without significant hypoglycemia. Stricter glycemic targets would seem appropriate in patients recently diagnosed with diabetes, those who have a long life expectancy, and those who have not yet developed significant cardiovascular disease.⁹

However, in patients who already have developed advanced microvascular and macrovascular complications, who have long-standing diabetes, who have a history of severe hypoglycemia (or hypoglycemia unawareness), or who have a limited life expectancy or numerous adverse comorbidities, a less strict glycemic target (hemoglobin A_1c < 8%) may be more appropriate.⁹

CARDIOVASCULAR RISK, HYPOGLYCEMIA, AND ATTAINING GLYCEMIC TARGETS

Metformin, in the absence of contraindications or intolerability, is generally the recommended first-line therapy to manage glycemia in patients with type 2 diabetes mellitus.^10,11 However, there are only limited data to direct clinicians as to which antidiabetic medication to use if further therapy is required to obtain glycemic control.

Much of the cardiovascular and mortality risk associated with aggressive diabetes management (ie, lower A_1c targets) is related to hypoglycemia. Thus, antidiabetic therapies that pose no risk or only a low risk of hypoglycemia should be chosen, particularly in older patients and in those with known cardiovascular disease. This may allow for better glycemic control without the risk of hypoglycemia and adverse cardiovascular outcomes.

However, in practice, clinicians continue to use a sulfonylurea as the second-line agent. Although sulfonylureas may appear to be a great option because of their low cost, they are associated with a higher risk of hypoglycemic episodes than other classes of diabetes drugs. We need to consider the frequency and cost of hypoglycemic episodes and the potential morbidity associated with them, because these episodes are a barrier to our efforts to achieve better glycemic control.

Budnitz et al¹² reported that from 2007 through 2009, in US adults age 65 and older, insulins were implicated in 13.9% of hospitalizations related to adverse drug events, and oral hypoglycemic agents (ie, insulin secretagogues) in 10.7%.

Quilliam et al¹³ reported that hypoglycemia resulted in a mean cost of $17,564 for an inpatient admission, $1,387 for an emergency department visit, and $394 for an outpatient visit. Thus, the cost savings associated with prescribing a sulfonylurea vs one of the newer oral antidiabetic agents that do not increase the risk of hypoglycemia (unless used concurrently with insulin or an insulin secretagogue) can quickly be eroded by severe hypoglycemic episodes requiring medical care.

Moreover, once patients start to experience hypoglycemic episodes, they are very reluctant, as are their physicians, to intensify therapy, even if it is indicated by their elevated A_1c.

There are now seven classes of oral antidiabetic therapies other than insulin secretagogues (ie, other than sulfonylureas and the meglitinides nateglinide and repaglinide), as well as a few noninsulin injectable therapies (glucagon-like peptide-1 agonists), that are not associated with hypoglycemia. We believe these agents should be tried before prescribing an agent that carries the risk of hypoglycemia (ie, sulfonylureas).

If agents that do not cause hypoglycemia are used, more-aggressive glycemic targets may be achieved safely. The ACCORD study,² which included patients at high cardiovascular risk and aimed at an aggressive glycemic target of 6%, may have yielded much different results had agents that carry a high risk of hypoglycemia been excluded.

Of importance, cardiovascular risk is also influenced by the common comorbidities seen in patients with diabetes, such as hypertension and hypercholesterolemia. Intensive, multifactorial interventions that address not only glycemic control but also blood pressure and lipids and that include low-dose aspirin therapy have been shown to lower the risk of death from cardiovascular causes and the risk of cardiovascular events.¹⁴ Likewise, smoking cessation is very important in reducing cardiovascular risk, especially in patients with diabetes.¹⁵

CLINICAL TRIALS IN CONTEXT

In conclusion, there is more to diabetes management than cardiovascular complications. Clearly, improved glycemic control decreases the risk of retinopathy, nephropathy, and neuropathy in patients with type 1 and type 2 diabetes. The DCCT and UKPDS extension studies further found that excellent glycemic control decreases rates of cardiac events.

The best way to treat diabetes may be different in otherwise healthy younger patients who have yet to develop significant complications than it is in older patients known to have cardiovascular disease or several risk factors for cardiovascular events. The available evidence suggests it would be reasonable to aim for stricter glycemic targets in the younger patients and less stringent targets in the older patients, particularly in those with long-standing diabetes who have already developed significant micro- and macrovascular complications.

We should interpret clinical trials within their narrow clinical context, emphasizing the actual population of patients included in the study, so as to avoid the inappropriate extrapolation of the results to all.

Diabetes mellitus and its management have become the center of controversy in recent years. More emphasis is being placed on the potential for adverse cardiovascular outcomes with more aggressive glycemic control as well as on the potential for adverse cardiovascular events with newer antidiabetic therapies, and less on the importance of glycemic control, particularly early in the disease course.

See related article

Although it is important to take new data into consideration when managing diabetes, it appears that the results of recent clinical trials are being misinterpreted and incorrectly applied to the wrong patient populations, and in the process, the results of older landmark clinical trials are being neglected. Inadequate glycemic control not only plays a role in cardiovascular risk, it also remains the leading cause of blindness, kidney failure, and nontraumatic lower-limb amputations in the United States.¹

Although we need to recognize the potential for adverse cardiovascular outcomes with diabetes and its management, we cannot lose sight of the big picture—ie, that inadequate glycemic control confers both microvascular and macrovascular risk, and that the available data show that restoring near-euglycemia in patients with diabetes considerably reduces the risk of microvascular and macrovascular complications.

Several recently published clinical trials—the Action to Control Cardiovascular Risk in Diabetes (ACCORD),² the Veterans Affairs Diabetes Trial (VADT),³ and the Action in Diabetes and Vascular Disease (ADVANCE)⁴—failed to demonstrate improved cardiovascular outcomes with improved glycemic control. However, we should not take this to mean that glycemic control is unimportant.

In this article, we will discuss why the results of these recent clinical trials are not valid for the general population of patients with diabetes. We will review evidence from landmark clinical trials that clearly demonstrates that better glycemic control reduces both microvascular and macrovascular complications of diabetes (the “glucose hypothesis”). We contend that excellent glycemic control clearly decreases the microvascular complications of diabetes, and that results from long-term follow-up studies in both type 1 and type 2 diabetes show reduced rates of heart attack and stroke in patients treated intensively earlier in the course of their disease.^5,6

EVIDENCE FOR THE GLUCOSE HYPOTHESIS

Diabetes Control and Complications Trial

The first major trial demonstrating that improved glycemic control provides benefit was the Diabetes Control and Complications Trial (DCCT).⁷ This study enrolled 1,441 patients with insulin-dependent diabetes mellitus, 726 of whom had no retinopathy at baseline (the primary-prevention cohort) and 715 of whom had mild retinopathy (the secondary-intervention cohort).

Patients were randomly assigned to intensive therapy (three or more insulin injections per day or an insulin pump) or to conventional therapy with one or two daily insulin injections. They were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.

During the study, the hemoglobin A_1c level averaged 9% in the control group and 7% in the intensively treated group. The cumulative incidence of retinopathy was defined as a change of three steps or more on fundus photography that was sustained over a 6-month period.

Effect on retinopathy. At study completion, the cumulative incidence of retinopathy in the intensive-therapy group was approximately 50% less than in the conventional-therapy group. Intensive therapy reduced the adjusted mean risk of retinopathy by 76% (95% confidence interval [CI] 62%–85%) in the primary-prevention cohort. In the secondary-prevention cohort, intensive therapy reduced the average risk of progression by 54% (95% CI 39%–66%). Intensive therapy reduced the adjusted risk of proliferative or severe nonproliferative retinopathy by 47% (P = .011) and that of treatment with photocoagulation by 56% (P = .002).

Effect on nephropathy. Intensive therapy reduced the mean adjusted risk of microalbuminuria by 34% (P = .04) in the primary-prevention cohort and by 43% (P = .001) in the secondary-intervention cohort. The risk of macroalbuminuria was reduced by 56% (P = .01) in the secondary-intervention cohort.

Effect on neuropathy. In the patients in the primary-prevention cohort who did not have neuropathy at baseline, intensive therapy reduced the incidence of neuropathy at 5 years by 69% (to 3%, vs 10% in the conventional-therapy group; P = .006). Similarly, in the secondary-intervention cohort, intensive therapy reduced the incidence of clinical neuropathy at 5 years by 57% (to 7%, vs 16%; P < .001).

Effect on macrovascular events. In the initial trial, a nonsignificant 41% reduction in combined cardiovascular and peripheral vascular disease events was observed.

DCCT long-term follow-up

After DCCT concluded, the control and treatment groups’ hemoglobin A_1c levels converged to approximately 8%. The two groups were then followed to determine the long-term effects of their prior separation of glycemic levels on micro- and macrovascular out comes.⁵ More than 90% of the original DCCT patients were followed for a mean of 17 years.

Intensive treatment reduced the risk of any cardiovascular disease event by 42% (95% CI 9%–63%; P = .02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57% (95% CI 12%– 79%; P = .02). This result was observed despite separation of glucose control in the two groups only for the first 6.5 years. This beneficial effect of intensive early glycemic control has been termed metabolic memory.

United Kingdom Prospective Diabetes Study

A second major trial, the United Kingdom Prospective Diabetes Study (UKPDS),⁸ assessed the effect of excellent diabetes control on diabetes complications in patients with type 2 diabetes. A total of 3,867 patients newly diagnosed with type 2 diabetes, median age 54, who after 3 months of diet treatment had mean fasting plasma glucose concentrations of 110 to 270 mg/dL, were randomly assigned to an intensive policy (with a sulfonylurea or insulin or, if overweight, metformin) or a conventional policy with diet. The aim in the intensive group was a fasting plasma glucose less than 108 mg/dL. In the conventional group, the aim was the best achievable fasting plasma glucose with diet alone; drugs were added only if there were hyperglycemic symptoms or a fasting plasma glucose greater than 270 mg/dL.

Over 10 years, the median hemoglobin A_1c level was 7.0% (interquartile range 6.2%–8.2%) in the intensive group compared with 7.9% (6.9%–8.8%) in the conventional group. Compared with the conventional group, the risk of any diabetes-related end point was 12% lower in the intensive group (95% CI 1%–21%, P = .029), the risk of any diabetes-related death was 10% lower (−11% to 27%, P = .34), and the rate of all-cause mortality was 6% lower (−10% to 20%, P = .44). Most of the reduction in risk of any diabetes-related end point was from a 25% risk reduction (95% CI 7%–40%, P = .0099) in microvascular end points, including the need for retinal photocoagulation.

UKPDS long-term follow-up

In 2008, Holman et al published the results of long-term follow-up of patients included in the UKPDS.⁶ In posttrial monitoring, 3,277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires.

Between-group differences in hemoglobin A_1c levels were lost after the first year. However, in the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P = .04) and microvascular disease (24%, P = .001), while risk reductions for myocardial infarction (15%, P = .01) and death from any cause (13%, P = .007) emerged over time as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P = .01), myocardial infarction (33%, P = .005), and death from any cause (27%, P = .002).

The long-term follow-up to the UKPDS, like the long-term follow-up to the DCCT, demonstrated metabolic memory: that is, despite an early loss of glycemic differences after completion of the trial, a continued reduction in microvascular risk and an emergent risk reduction for myocardial infarction and death from any cause were observed.

These long-term randomized prospective trials in patients with type 1 and type 2 diabetes clearly show that the glucose hypothesis is in fact correct: intensive glucose control lowers the risk of both microvascular and macrovascular complications of diabetes.

IS THERE DISCORDANCE BETWEEN OLDER AND MORE RECENT TRIALS?

If the results of these older landmark clinical trials are true, why did the more recent clinical trials fail to show cardiovascular benefit with stricter glycemic control, and in one trial² demonstrate the potential for harm? (ACCORD² found an increased death rate in patients who received intensive therapy, targeting a hemoglobin A_1c below 6.0%.)

The answer lies in the populations studied. ACCORD,² VADT,³ and ADVANCE⁴ were performed in older patients with prior cardiac events or with several risk factors for cardiovascular events. The study populations were picked to increase the number of cardiac events in a short time frame. Therefore, extrapolating the results of these studies to the younger population of patients with diabetes, most of whom have yet to develop macrovascular disease, is inappropriate.

The available evidence suggests that early aggressive management of diabetes reduces the risk of macrovascular disease, but that this benefit is delayed. In the UKPDS and DCCT trials, it took 10 to 17 years to show cardiac benefit in younger patients.

The results of ACCORD,² VADT,³ and ADVANCE⁴ are important when considered in the correct clinical context. Two of these trials did demonstrate some microvascular benefit as a result of better glycemic control in older patients, many of whom had longstanding diabetes. These studies suggest that, in patients who already have established cardiovascular disease or have several risk factors for cardiovascular events, a less-strict glycemic target may be warranted.

These trials should not be interpreted as saying that glycemic control is unimportant in older patients at higher risk. Rather, they suggest that an individualized approach to diabetes management, supported by the most recent American Diabetes Association guidelines,⁹ is more appropriate.

Physicians may reasonably suggest a stricter A_1c goal (ie, < 6.5%) in certain patients if it can be achieved without significant hypoglycemia. Stricter glycemic targets would seem appropriate in patients recently diagnosed with diabetes, those who have a long life expectancy, and those who have not yet developed significant cardiovascular disease.⁹

However, in patients who already have developed advanced microvascular and macrovascular complications, who have long-standing diabetes, who have a history of severe hypoglycemia (or hypoglycemia unawareness), or who have a limited life expectancy or numerous adverse comorbidities, a less strict glycemic target (hemoglobin A_1c < 8%) may be more appropriate.⁹

CARDIOVASCULAR RISK, HYPOGLYCEMIA, AND ATTAINING GLYCEMIC TARGETS

Metformin, in the absence of contraindications or intolerability, is generally the recommended first-line therapy to manage glycemia in patients with type 2 diabetes mellitus.^10,11 However, there are only limited data to direct clinicians as to which antidiabetic medication to use if further therapy is required to obtain glycemic control.

Much of the cardiovascular and mortality risk associated with aggressive diabetes management (ie, lower A_1c targets) is related to hypoglycemia. Thus, antidiabetic therapies that pose no risk or only a low risk of hypoglycemia should be chosen, particularly in older patients and in those with known cardiovascular disease. This may allow for better glycemic control without the risk of hypoglycemia and adverse cardiovascular outcomes.

However, in practice, clinicians continue to use a sulfonylurea as the second-line agent. Although sulfonylureas may appear to be a great option because of their low cost, they are associated with a higher risk of hypoglycemic episodes than other classes of diabetes drugs. We need to consider the frequency and cost of hypoglycemic episodes and the potential morbidity associated with them, because these episodes are a barrier to our efforts to achieve better glycemic control.

Budnitz et al¹² reported that from 2007 through 2009, in US adults age 65 and older, insulins were implicated in 13.9% of hospitalizations related to adverse drug events, and oral hypoglycemic agents (ie, insulin secretagogues) in 10.7%.

Quilliam et al¹³ reported that hypoglycemia resulted in a mean cost of $17,564 for an inpatient admission, $1,387 for an emergency department visit, and $394 for an outpatient visit. Thus, the cost savings associated with prescribing a sulfonylurea vs one of the newer oral antidiabetic agents that do not increase the risk of hypoglycemia (unless used concurrently with insulin or an insulin secretagogue) can quickly be eroded by severe hypoglycemic episodes requiring medical care.

Moreover, once patients start to experience hypoglycemic episodes, they are very reluctant, as are their physicians, to intensify therapy, even if it is indicated by their elevated A_1c.

There are now seven classes of oral antidiabetic therapies other than insulin secretagogues (ie, other than sulfonylureas and the meglitinides nateglinide and repaglinide), as well as a few noninsulin injectable therapies (glucagon-like peptide-1 agonists), that are not associated with hypoglycemia. We believe these agents should be tried before prescribing an agent that carries the risk of hypoglycemia (ie, sulfonylureas).

If agents that do not cause hypoglycemia are used, more-aggressive glycemic targets may be achieved safely. The ACCORD study,² which included patients at high cardiovascular risk and aimed at an aggressive glycemic target of 6%, may have yielded much different results had agents that carry a high risk of hypoglycemia been excluded.

Of importance, cardiovascular risk is also influenced by the common comorbidities seen in patients with diabetes, such as hypertension and hypercholesterolemia. Intensive, multifactorial interventions that address not only glycemic control but also blood pressure and lipids and that include low-dose aspirin therapy have been shown to lower the risk of death from cardiovascular causes and the risk of cardiovascular events.¹⁴ Likewise, smoking cessation is very important in reducing cardiovascular risk, especially in patients with diabetes.¹⁵

CLINICAL TRIALS IN CONTEXT

In conclusion, there is more to diabetes management than cardiovascular complications. Clearly, improved glycemic control decreases the risk of retinopathy, nephropathy, and neuropathy in patients with type 1 and type 2 diabetes. The DCCT and UKPDS extension studies further found that excellent glycemic control decreases rates of cardiac events.

The best way to treat diabetes may be different in otherwise healthy younger patients who have yet to develop significant complications than it is in older patients known to have cardiovascular disease or several risk factors for cardiovascular events. The available evidence suggests it would be reasonable to aim for stricter glycemic targets in the younger patients and less stringent targets in the older patients, particularly in those with long-standing diabetes who have already developed significant micro- and macrovascular complications.

We should interpret clinical trials within their narrow clinical context, emphasizing the actual population of patients included in the study, so as to avoid the inappropriate extrapolation of the results to all.

Introduction

Autism spectrum disorder is a neurodevelopmental condition characterized by a heterogeneous grouping of social-communication impairments and behavioral phenomena that are observed in early development and often accompanied by an array of co-occurring issues. The prevalence of autism spectrum disorder (ASD) has risen markedly in the last several years (1 in 68 per a 2014 CDC estimate), and the evidence base for early intervention and other treatment strategies supports the idea that a timely and appropriate diagnosis is critical for promoting positive outcomes for children and their families.

With ASD, there can be wide variety in a young child’s presenting symptoms. Although some youth clearly manifest the hallmark features of ASD, ever-changing development, complicated cognitive profiles, family difficulties, co-occurring mental health problems, and evolving nosology (such as DSM changes) can contribute to the difficulty providers encounter in fully interpreting and identifying ASD symptoms in the course of a typical primary care visit. This case example outlines assessment and diagnostic strategies that may help pediatricians to better understand the complexities of diagnosis, assessment, and treatment for children suspected of having ASD. Ideally, a diagnostic evaluation would quickly follow a standardized screening tool that is positive for concern for ASD (such as the Modified Checklist for Autism in Toddlers – Revised) between the ages of 18 and 24 months.

Case summary

Everett is a 4-year-old boy who presents to an autism diagnostic clinic after his parents expressed concerns about his behavior. Everett is described to be a rigid, stubborn, strong-willed, and easily frustrated boy who began to exhibit aggressive behaviors at 18 months of age. He continues to have almost daily temper tantrums. Notably, Everett did not begin to use single words with communicative intent until he was 24 months old. He will often repeat words nonfunctionally and utter nonsensical verbalizations while spinning in circles and rocking back and forth. Everett enjoys being around peers but has difficulties engaging appropriately with other children, exhibiting poor physical boundaries. Everett’s hearing and vision were previously tested to be without deficit, and there is no history of seizure activity or indication of an underlying metabolic disorder.

Discussion

Everett presents with some signs and symptoms to suggest ASD (namely his communication and language impairments accompanied by some atypical social relatedness and repetitive behaviors). His presentation, however, has many characteristics that while common to ASD are not entirely specific to the diagnosis in a preschooler, and could occur with other disorders. For example, Everett’s social difficulties could be the result of an emerging behavioral disorder (an oppositional defiant disorder) or a primary expressive language disorder, which may manifest with frustration intolerance due to communication difficulties.

With children like Everett, a comprehensive autism diagnostic assessment should be obtained and preferably be comprised of a minimum of two components – a caregiver interview and an observational assessment ideally conducted by an experienced clinical interdisciplinary team. Additionally, evaluations of adaptive skills, cognitive profile, family functioning, social-emotional/behavioral functioning, and sensory issues can be useful to inform treatment planning and diagnosis. Ultimately, the diagnosis of ASD is made after clinicians integrate available information and fully consider the range of differential diagnoses. Clinicians who may participate in the diagnostic process include developmental pediatricians, child psychiatrists, clinical psychologists, speech-language pathologists, and other allied health professionals.

Clinical guidelines suggest that gathering a thorough developmental history, assessing for the characteristic impairments that support an ASD diagnosis, and establishing current levels of functioning can be performed using the semistructured Autism Diagnostic Interview – Revised (ADI-R) with primary caregivers. Information about a child’s social interactions also can be obtained with the use of the Social Responsiveness Scale (SRS), which can yield multi-informant data that helps to capture a youth’s functioning and peer interactions in different settings, including home and school.

The observational assessment ideally utilizes the Autism Diagnostic Observation Schedule (ADOS), a standardized instrument that can evaluate domains of reciprocal social interaction, communication, restricted interests, and repetitive behaviors in a developmentally informed manner. Clinicians should be mindful that certain behaviors may not be displayed during the diagnostic evaluation, and as such, scoring on the ADOS should be integrated with other sources of information and interpreted within a developmental framework; no single result on one instrument is sufficient to make or break an autism diagnosis.

The above-mentioned tools were used in Everett’s assessment. Appraising the collected data, his scoring on the ADOS suggested an autism diagnosis, but information from the ADI-R and SRS were not conclusive. To further evaluate Everett, we incorporated a broad developmental evaluation tool, the Mullen Scales of Early Learning, which provided us with a lens through which to interpret his profile of impairments and strengths. Everett scored with average to above-average skills across all domains, which helped us conceptualize that his social, language, and behavioral struggles were not the result of a global developmental delay or intellectual disability.

Additionally, Everett’s family completed the Vineland Adaptive Behavior Scales (his adaptive socialization skills were a relative weakness, and motor skills were a strength) and Child Behavior Checklists, which revealed the endorsement of emotionally reactive and aggressive behavior symptoms from both parents. Everett’s parents’ mental wellness was assessed with Adult Behavior Checklists in order to provide informed family-based treatment recommendations.

In Everett’s evaluation, enduring challenges in the core symptom domains characterizing ASD were noted. His atypical social affect, limited social awareness, and repetitive patterns of behavior provided evidence that Everett met diagnostic criteria for ASD. Also noted were protective factors that promoted his well-being (he’s verbal, has the capacity to play imaginatively, presents with a supportive family, and demonstrates no significant cognitive deficiencies), which were incorporated into our treatment recommendations. Recommendations included enrollment in structured educational and behavioral interventions, and corresponding parent training treatments to help his caregivers manage his disruptive behaviors while reducing the risk for the development of further emotional/behavioral problems in the future.

Everett’s ASD diagnosis also warranted a referral for genetic testing and/or counseling to help the family to obtain information about the etiology of the disorder, screen for other conditions, and help guide appropriate medical management. There were no other indications to pursue additional medical, imaging, or neurological consultations.

Clinical pearl

For some children, the diagnosis of ASD is unclear. Problems arise in making an accurate diagnosis for a variety of reasons, and fully appreciating a child’s (or adolescent’s) developmental challenges can be difficult, especially given the considerable symptom overlap ASD has with other learning, medical, cognitive, or mental health diagnoses. These children require a diagnostic evaluation using a family-focused and culturally sensitive multidisciplinary approach that incorporates standardized tools. As a primary care provider, it can often be difficult to tease out symptoms and have the time to do a thorough assessment; primary providers should be aware of their local assessment expert resources and referral options.

Jeremiah Dickerson, M.D., a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. Dr. Dickerson is the director of the university’s autism diagnostic clinic. Contact Dr. Dickerson at [email protected].

Introduction

Autism spectrum disorder is a neurodevelopmental condition characterized by a heterogeneous grouping of social-communication impairments and behavioral phenomena that are observed in early development and often accompanied by an array of co-occurring issues. The prevalence of autism spectrum disorder (ASD) has risen markedly in the last several years (1 in 68 per a 2014 CDC estimate), and the evidence base for early intervention and other treatment strategies supports the idea that a timely and appropriate diagnosis is critical for promoting positive outcomes for children and their families.

With ASD, there can be wide variety in a young child’s presenting symptoms. Although some youth clearly manifest the hallmark features of ASD, ever-changing development, complicated cognitive profiles, family difficulties, co-occurring mental health problems, and evolving nosology (such as DSM changes) can contribute to the difficulty providers encounter in fully interpreting and identifying ASD symptoms in the course of a typical primary care visit. This case example outlines assessment and diagnostic strategies that may help pediatricians to better understand the complexities of diagnosis, assessment, and treatment for children suspected of having ASD. Ideally, a diagnostic evaluation would quickly follow a standardized screening tool that is positive for concern for ASD (such as the Modified Checklist for Autism in Toddlers – Revised) between the ages of 18 and 24 months.

Case summary

Everett is a 4-year-old boy who presents to an autism diagnostic clinic after his parents expressed concerns about his behavior. Everett is described to be a rigid, stubborn, strong-willed, and easily frustrated boy who began to exhibit aggressive behaviors at 18 months of age. He continues to have almost daily temper tantrums. Notably, Everett did not begin to use single words with communicative intent until he was 24 months old. He will often repeat words nonfunctionally and utter nonsensical verbalizations while spinning in circles and rocking back and forth. Everett enjoys being around peers but has difficulties engaging appropriately with other children, exhibiting poor physical boundaries. Everett’s hearing and vision were previously tested to be without deficit, and there is no history of seizure activity or indication of an underlying metabolic disorder.

Discussion

Everett presents with some signs and symptoms to suggest ASD (namely his communication and language impairments accompanied by some atypical social relatedness and repetitive behaviors). His presentation, however, has many characteristics that while common to ASD are not entirely specific to the diagnosis in a preschooler, and could occur with other disorders. For example, Everett’s social difficulties could be the result of an emerging behavioral disorder (an oppositional defiant disorder) or a primary expressive language disorder, which may manifest with frustration intolerance due to communication difficulties.

With children like Everett, a comprehensive autism diagnostic assessment should be obtained and preferably be comprised of a minimum of two components – a caregiver interview and an observational assessment ideally conducted by an experienced clinical interdisciplinary team. Additionally, evaluations of adaptive skills, cognitive profile, family functioning, social-emotional/behavioral functioning, and sensory issues can be useful to inform treatment planning and diagnosis. Ultimately, the diagnosis of ASD is made after clinicians integrate available information and fully consider the range of differential diagnoses. Clinicians who may participate in the diagnostic process include developmental pediatricians, child psychiatrists, clinical psychologists, speech-language pathologists, and other allied health professionals.

Clinical guidelines suggest that gathering a thorough developmental history, assessing for the characteristic impairments that support an ASD diagnosis, and establishing current levels of functioning can be performed using the semistructured Autism Diagnostic Interview – Revised (ADI-R) with primary caregivers. Information about a child’s social interactions also can be obtained with the use of the Social Responsiveness Scale (SRS), which can yield multi-informant data that helps to capture a youth’s functioning and peer interactions in different settings, including home and school.

The observational assessment ideally utilizes the Autism Diagnostic Observation Schedule (ADOS), a standardized instrument that can evaluate domains of reciprocal social interaction, communication, restricted interests, and repetitive behaviors in a developmentally informed manner. Clinicians should be mindful that certain behaviors may not be displayed during the diagnostic evaluation, and as such, scoring on the ADOS should be integrated with other sources of information and interpreted within a developmental framework; no single result on one instrument is sufficient to make or break an autism diagnosis.

The above-mentioned tools were used in Everett’s assessment. Appraising the collected data, his scoring on the ADOS suggested an autism diagnosis, but information from the ADI-R and SRS were not conclusive. To further evaluate Everett, we incorporated a broad developmental evaluation tool, the Mullen Scales of Early Learning, which provided us with a lens through which to interpret his profile of impairments and strengths. Everett scored with average to above-average skills across all domains, which helped us conceptualize that his social, language, and behavioral struggles were not the result of a global developmental delay or intellectual disability.

Additionally, Everett’s family completed the Vineland Adaptive Behavior Scales (his adaptive socialization skills were a relative weakness, and motor skills were a strength) and Child Behavior Checklists, which revealed the endorsement of emotionally reactive and aggressive behavior symptoms from both parents. Everett’s parents’ mental wellness was assessed with Adult Behavior Checklists in order to provide informed family-based treatment recommendations.

In Everett’s evaluation, enduring challenges in the core symptom domains characterizing ASD were noted. His atypical social affect, limited social awareness, and repetitive patterns of behavior provided evidence that Everett met diagnostic criteria for ASD. Also noted were protective factors that promoted his well-being (he’s verbal, has the capacity to play imaginatively, presents with a supportive family, and demonstrates no significant cognitive deficiencies), which were incorporated into our treatment recommendations. Recommendations included enrollment in structured educational and behavioral interventions, and corresponding parent training treatments to help his caregivers manage his disruptive behaviors while reducing the risk for the development of further emotional/behavioral problems in the future.

Everett’s ASD diagnosis also warranted a referral for genetic testing and/or counseling to help the family to obtain information about the etiology of the disorder, screen for other conditions, and help guide appropriate medical management. There were no other indications to pursue additional medical, imaging, or neurological consultations.

Clinical pearl

For some children, the diagnosis of ASD is unclear. Problems arise in making an accurate diagnosis for a variety of reasons, and fully appreciating a child’s (or adolescent’s) developmental challenges can be difficult, especially given the considerable symptom overlap ASD has with other learning, medical, cognitive, or mental health diagnoses. These children require a diagnostic evaluation using a family-focused and culturally sensitive multidisciplinary approach that incorporates standardized tools. As a primary care provider, it can often be difficult to tease out symptoms and have the time to do a thorough assessment; primary providers should be aware of their local assessment expert resources and referral options.

Jeremiah Dickerson, M.D., a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. Dr. Dickerson is the director of the university’s autism diagnostic clinic. Contact Dr. Dickerson at [email protected].

Introduction

Autism spectrum disorder is a neurodevelopmental condition characterized by a heterogeneous grouping of social-communication impairments and behavioral phenomena that are observed in early development and often accompanied by an array of co-occurring issues. The prevalence of autism spectrum disorder (ASD) has risen markedly in the last several years (1 in 68 per a 2014 CDC estimate), and the evidence base for early intervention and other treatment strategies supports the idea that a timely and appropriate diagnosis is critical for promoting positive outcomes for children and their families.

With ASD, there can be wide variety in a young child’s presenting symptoms. Although some youth clearly manifest the hallmark features of ASD, ever-changing development, complicated cognitive profiles, family difficulties, co-occurring mental health problems, and evolving nosology (such as DSM changes) can contribute to the difficulty providers encounter in fully interpreting and identifying ASD symptoms in the course of a typical primary care visit. This case example outlines assessment and diagnostic strategies that may help pediatricians to better understand the complexities of diagnosis, assessment, and treatment for children suspected of having ASD. Ideally, a diagnostic evaluation would quickly follow a standardized screening tool that is positive for concern for ASD (such as the Modified Checklist for Autism in Toddlers – Revised) between the ages of 18 and 24 months.

Case summary

Everett is a 4-year-old boy who presents to an autism diagnostic clinic after his parents expressed concerns about his behavior. Everett is described to be a rigid, stubborn, strong-willed, and easily frustrated boy who began to exhibit aggressive behaviors at 18 months of age. He continues to have almost daily temper tantrums. Notably, Everett did not begin to use single words with communicative intent until he was 24 months old. He will often repeat words nonfunctionally and utter nonsensical verbalizations while spinning in circles and rocking back and forth. Everett enjoys being around peers but has difficulties engaging appropriately with other children, exhibiting poor physical boundaries. Everett’s hearing and vision were previously tested to be without deficit, and there is no history of seizure activity or indication of an underlying metabolic disorder.

Discussion

Everett presents with some signs and symptoms to suggest ASD (namely his communication and language impairments accompanied by some atypical social relatedness and repetitive behaviors). His presentation, however, has many characteristics that while common to ASD are not entirely specific to the diagnosis in a preschooler, and could occur with other disorders. For example, Everett’s social difficulties could be the result of an emerging behavioral disorder (an oppositional defiant disorder) or a primary expressive language disorder, which may manifest with frustration intolerance due to communication difficulties.

With children like Everett, a comprehensive autism diagnostic assessment should be obtained and preferably be comprised of a minimum of two components – a caregiver interview and an observational assessment ideally conducted by an experienced clinical interdisciplinary team. Additionally, evaluations of adaptive skills, cognitive profile, family functioning, social-emotional/behavioral functioning, and sensory issues can be useful to inform treatment planning and diagnosis. Ultimately, the diagnosis of ASD is made after clinicians integrate available information and fully consider the range of differential diagnoses. Clinicians who may participate in the diagnostic process include developmental pediatricians, child psychiatrists, clinical psychologists, speech-language pathologists, and other allied health professionals.

Clinical guidelines suggest that gathering a thorough developmental history, assessing for the characteristic impairments that support an ASD diagnosis, and establishing current levels of functioning can be performed using the semistructured Autism Diagnostic Interview – Revised (ADI-R) with primary caregivers. Information about a child’s social interactions also can be obtained with the use of the Social Responsiveness Scale (SRS), which can yield multi-informant data that helps to capture a youth’s functioning and peer interactions in different settings, including home and school.

The observational assessment ideally utilizes the Autism Diagnostic Observation Schedule (ADOS), a standardized instrument that can evaluate domains of reciprocal social interaction, communication, restricted interests, and repetitive behaviors in a developmentally informed manner. Clinicians should be mindful that certain behaviors may not be displayed during the diagnostic evaluation, and as such, scoring on the ADOS should be integrated with other sources of information and interpreted within a developmental framework; no single result on one instrument is sufficient to make or break an autism diagnosis.

The above-mentioned tools were used in Everett’s assessment. Appraising the collected data, his scoring on the ADOS suggested an autism diagnosis, but information from the ADI-R and SRS were not conclusive. To further evaluate Everett, we incorporated a broad developmental evaluation tool, the Mullen Scales of Early Learning, which provided us with a lens through which to interpret his profile of impairments and strengths. Everett scored with average to above-average skills across all domains, which helped us conceptualize that his social, language, and behavioral struggles were not the result of a global developmental delay or intellectual disability.

Additionally, Everett’s family completed the Vineland Adaptive Behavior Scales (his adaptive socialization skills were a relative weakness, and motor skills were a strength) and Child Behavior Checklists, which revealed the endorsement of emotionally reactive and aggressive behavior symptoms from both parents. Everett’s parents’ mental wellness was assessed with Adult Behavior Checklists in order to provide informed family-based treatment recommendations.

In Everett’s evaluation, enduring challenges in the core symptom domains characterizing ASD were noted. His atypical social affect, limited social awareness, and repetitive patterns of behavior provided evidence that Everett met diagnostic criteria for ASD. Also noted were protective factors that promoted his well-being (he’s verbal, has the capacity to play imaginatively, presents with a supportive family, and demonstrates no significant cognitive deficiencies), which were incorporated into our treatment recommendations. Recommendations included enrollment in structured educational and behavioral interventions, and corresponding parent training treatments to help his caregivers manage his disruptive behaviors while reducing the risk for the development of further emotional/behavioral problems in the future.

Everett’s ASD diagnosis also warranted a referral for genetic testing and/or counseling to help the family to obtain information about the etiology of the disorder, screen for other conditions, and help guide appropriate medical management. There were no other indications to pursue additional medical, imaging, or neurological consultations.

Clinical pearl

For some children, the diagnosis of ASD is unclear. Problems arise in making an accurate diagnosis for a variety of reasons, and fully appreciating a child’s (or adolescent’s) developmental challenges can be difficult, especially given the considerable symptom overlap ASD has with other learning, medical, cognitive, or mental health diagnoses. These children require a diagnostic evaluation using a family-focused and culturally sensitive multidisciplinary approach that incorporates standardized tools. As a primary care provider, it can often be difficult to tease out symptoms and have the time to do a thorough assessment; primary providers should be aware of their local assessment expert resources and referral options.

Jeremiah Dickerson, M.D., a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. Dr. Dickerson is the director of the university’s autism diagnostic clinic. Contact Dr. Dickerson at [email protected].

Obesity not only increases a patient’s lifetime risk of numerous chronic conditions, such as diabetes, heart disease and kidney disease, but it also is a major health issue during pregnancy. Women who are obese in pregnancy have a significantly higher chance of developing adverse perinatal outcomes and experiencing various complications that affect both their health and that of their babies.

With an ever-increasing population of overweight and obese women of reproductive age, as key caregivers for women, we must reexamine our approaches and do much more than microfocusing on a woman’s pre- and postdelivery health. We must play a more active role in helping our patients establish and maintain a healthy lifestyle – one that will help ward off and reduce the incidence of this concerning condition.

Over the previous two Master Class installments on obstetrics, we discussed the extent of the obesity epidemic and its link to diabetes, the alarming number of infants, children, and adolescents who are obese, and the implications of these societal and medical trends for ob.gyns.

In the July Master Class, we discussed the importance of appropriately counseling patients on healthy weight gain and physical activity in pregnancy. Because ob.gyns. may be the only health care professionals that many women may see, it is becoming more important that we help our patients and their children attain and maintain positive health and well-being.

In our September installment, Dr. Thomas R. Moore looked at obesity trends through the lens of the Barker Hypothesis, which got us thinking more than 3 decades ago about the role of intrauterine environment in short- and long-term health of offspring. Dr. Moore discussed how obesity in pregnancy appears to program offspring for downstream cardiovascular risk in adulthood.

He told us that we must not only liberally treat gestational diabetes and optimize glucose control during pregnancy, but, most importantly, we also must emphasize to women the importance of having healthy weights at the time of conception.

This month’s Master Class examines this latter concept in more depth. Dr. Patrick Catalano, professor in the department of obstetrics and gynecology and director of the Center for Reproductive Health at MetroHealth Medical Center, Case Western Reserve University, Cleveland, has been at the forefront of research on the physiologic impact of obesity on the placenta and the fetus, and on approaches for addressing maternal obesity and improving perinatal outcomes.

Dr. Catalano explains here why weight loss before pregnancy appears to be important for preventing adverse perinatal outcomes and breaking the intergenerational transfer of obesity.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Obesity not only increases a patient’s lifetime risk of numerous chronic conditions, such as diabetes, heart disease and kidney disease, but it also is a major health issue during pregnancy. Women who are obese in pregnancy have a significantly higher chance of developing adverse perinatal outcomes and experiencing various complications that affect both their health and that of their babies.

With an ever-increasing population of overweight and obese women of reproductive age, as key caregivers for women, we must reexamine our approaches and do much more than microfocusing on a woman’s pre- and postdelivery health. We must play a more active role in helping our patients establish and maintain a healthy lifestyle – one that will help ward off and reduce the incidence of this concerning condition.

Over the previous two Master Class installments on obstetrics, we discussed the extent of the obesity epidemic and its link to diabetes, the alarming number of infants, children, and adolescents who are obese, and the implications of these societal and medical trends for ob.gyns.

In the July Master Class, we discussed the importance of appropriately counseling patients on healthy weight gain and physical activity in pregnancy. Because ob.gyns. may be the only health care professionals that many women may see, it is becoming more important that we help our patients and their children attain and maintain positive health and well-being.

In our September installment, Dr. Thomas R. Moore looked at obesity trends through the lens of the Barker Hypothesis, which got us thinking more than 3 decades ago about the role of intrauterine environment in short- and long-term health of offspring. Dr. Moore discussed how obesity in pregnancy appears to program offspring for downstream cardiovascular risk in adulthood.

He told us that we must not only liberally treat gestational diabetes and optimize glucose control during pregnancy, but, most importantly, we also must emphasize to women the importance of having healthy weights at the time of conception.

This month’s Master Class examines this latter concept in more depth. Dr. Patrick Catalano, professor in the department of obstetrics and gynecology and director of the Center for Reproductive Health at MetroHealth Medical Center, Case Western Reserve University, Cleveland, has been at the forefront of research on the physiologic impact of obesity on the placenta and the fetus, and on approaches for addressing maternal obesity and improving perinatal outcomes.

Dr. Catalano explains here why weight loss before pregnancy appears to be important for preventing adverse perinatal outcomes and breaking the intergenerational transfer of obesity.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Obesity not only increases a patient’s lifetime risk of numerous chronic conditions, such as diabetes, heart disease and kidney disease, but it also is a major health issue during pregnancy. Women who are obese in pregnancy have a significantly higher chance of developing adverse perinatal outcomes and experiencing various complications that affect both their health and that of their babies.

With an ever-increasing population of overweight and obese women of reproductive age, as key caregivers for women, we must reexamine our approaches and do much more than microfocusing on a woman’s pre- and postdelivery health. We must play a more active role in helping our patients establish and maintain a healthy lifestyle – one that will help ward off and reduce the incidence of this concerning condition.

Over the previous two Master Class installments on obstetrics, we discussed the extent of the obesity epidemic and its link to diabetes, the alarming number of infants, children, and adolescents who are obese, and the implications of these societal and medical trends for ob.gyns.

In the July Master Class, we discussed the importance of appropriately counseling patients on healthy weight gain and physical activity in pregnancy. Because ob.gyns. may be the only health care professionals that many women may see, it is becoming more important that we help our patients and their children attain and maintain positive health and well-being.

In our September installment, Dr. Thomas R. Moore looked at obesity trends through the lens of the Barker Hypothesis, which got us thinking more than 3 decades ago about the role of intrauterine environment in short- and long-term health of offspring. Dr. Moore discussed how obesity in pregnancy appears to program offspring for downstream cardiovascular risk in adulthood.

He told us that we must not only liberally treat gestational diabetes and optimize glucose control during pregnancy, but, most importantly, we also must emphasize to women the importance of having healthy weights at the time of conception.

This month’s Master Class examines this latter concept in more depth. Dr. Patrick Catalano, professor in the department of obstetrics and gynecology and director of the Center for Reproductive Health at MetroHealth Medical Center, Case Western Reserve University, Cleveland, has been at the forefront of research on the physiologic impact of obesity on the placenta and the fetus, and on approaches for addressing maternal obesity and improving perinatal outcomes.

Dr. Catalano explains here why weight loss before pregnancy appears to be important for preventing adverse perinatal outcomes and breaking the intergenerational transfer of obesity.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].